US5412110A - Enzymatic process to separate racemic mixtures of delta valerolactones - Google Patents

Enzymatic process to separate racemic mixtures of delta valerolactones Download PDF

Info

Publication number
US5412110A
US5412110A US07/936,782 US93678292A US5412110A US 5412110 A US5412110 A US 5412110A US 93678292 A US93678292 A US 93678292A US 5412110 A US5412110 A US 5412110A
Authority
US
United States
Prior art keywords
formula
delta
valerolactone
beta
enantiomerically pure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US07/936,782
Other languages
English (en)
Inventor
Peter Pochlauer
Marion Wagner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chemie Linz GmbH
Original Assignee
Chemie Linz GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chemie Linz GmbH filed Critical Chemie Linz GmbH
Assigned to CHEMIE LINZ GESELLSCHAFT M.B.H. reassignment CHEMIE LINZ GESELLSCHAFT M.B.H. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: POCHLAUER, PETER, WAGNER, MARION
Application granted granted Critical
Publication of US5412110A publication Critical patent/US5412110A/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02—Oxygen as only ring hetero atoms
    • C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C12P41/004—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction

Definitions

  • reaction sequence 1 starting from methyl acetoacetate, a racemic mixture of a (2RS,3RS,5SR)-2-hexyl-3-hydroxy-5-undecyl-delta-valerolactone is produced as the intermediate product, which is converted by means of several steps into race-(2RS,3RS,5SR)-5-benzyloxy-2-hexyl-3-hydroxyhexadecanoic acid.
  • the resolution of racemates takes place through the formation of a salt with the aid of an enantiomerically pure amine, thus separating the (2S,3S,5R) enantiomer from the (2R,3R,5S)-enantiomer.
  • enantiomerically pure 3-hydroxytetradecanoic acid ester is converted by way of several steps into enantiomerically pure 5-((R)-3-benzyloxy-1-hydeoxytetradecylidene)-2,2-dimethyl-m-dioxan-4,6-dione, which is cycled without any racemation into (R)-5,6-dihydro-6-undecyl-2H-pyran-2,4(3H)-dione, and is left to react further of several steps into enantiomerically pure oxetanohe.
  • a racemic mixture of beta-hydroxy-delta-valerolactones or of beta-acyloxy-delta-valerolactones, as described above, is esterified or hydrolyzed selectively by using a hydrolase, one obtains in a simple manner a mixture of an enantiomerically pure (2S,3S,5R)-beta-hydroxy-delta-valerolactone with an enantiomerically pure (2R,3R,5S)-beta-acyloxy-delta-valerolactone or a mixture of an enantiomerically pure (2R,3R,5S)-beta-hydroxy-delta-valerolactone with an enantiomerically pure (2S,3S,5R)-beta-acyloxy-delta-valerolactone, which can be separated then in a very simple manner.
  • the reaction comes surprisingly completely roan end after conversion of one of the enantiomers, so that products of highest purity are obtained.
  • the desired enantiomerically pure oxetanones can be obtained, according to the method described in the ZA 91/1153 from the separated compounds, if necessary after splitting off of the acyl group.
  • reaction according to the invention is generally completed within a few hours, in some cases even within 1 to 2 hours, even though the beta-hydroxy-valerolactones, according to the invention, are substituted by alkyl chains or aryl groups, so that the reaction should run even much slower for steric reasons than that described in the EP-A-0 439 779.
  • the object of the invention is a process to separate racemic mixtures of a compound of the general formula ##STR1## in which R denotes hydrogen or an acyl group, and R 1 and R 2 denote independently of each other hydrogen, a straight chained or branched alkyl group having 4 to 20 C atoms, which can be penetrated by an oxygen atom in a position other than the alpha or beta position or denote an unsubstituted aralkyl group or an aralkyl group substituted by inert groups under the reaction conditions, provided that R 1 and R 2 do not denote simultaneously hydrogen, which is characterized by the fact that the racemic mixture of a compound of the general formula I is introduced in a diluent and in the presence of a hydrolase and, in the case that R in the general formula I denotes hydrogen in the presence of an esterifying agent, is left to react, whereby a reaction mixture is produced that contains an enantiomerically pure beta-hydroxy-delta-valerolactone and
  • racemic mixture of general formula I are understood not only mixtures, which contain the enantiomer in a ratio of 1:1, but also mixtures, which contain the enantiomers in any arbitrary composition, in which, therefore, one of the enantiomers is enriched.
  • R denotes hydrogen or an acyl group, preferably hydrogen.
  • An acyl group is a group of the general formula --CO-- 3 , in which R 3 denotes an unsubstituted or by groups which are inert under the reaction conditions substituted alkyl or aryl group, preferably an unsubstituted alkyl group having 1 to 6 C atoms, quite preferably having 1 to 4 C atoms.
  • R 1 and R 2 denote independently of each other hydrogen, where R 1 and R 2 do not denote simultaneously hydrogen; an alkyl group having 4 to 20, preferably having 4 to 17 C atoms, which is straight chained or branched, preferably however straight chained; an alkyl group having 4 to 20, preferably having 4 to 17 C atoms, which is straight chained or branched and which is penetrated by an oxygen atom in a position other than the alpha or beta position; or an unsubstituted aralkyl group or an aralkyl group substituted by alkyl or alkoxy groups, where the alkyl or alkoxy groups exhibit preferably 1 to 6 C atoms.
  • R 1 and R 2 denote independently of each other hydrogen or alkyl groups, in particular R 1 and R 2 denote preferably alkyl groups.
  • An especially preferred beta-hydroxy-delta-valerolactone is one of the general formula I, in which R denotes hydrogen or an acyl group; R 1 denotes an alkyl group having 4 to 17 C atoms and R 2 denotes an alkyl group having 6 to 17 C atoms.
  • racemic mixtures of a compound of the general formula I, in which R denotes hydrogen can be prepared according to one of the methods disclosed in the ZA 91/1153.
  • Racemic mixtures of a compound, in which R denotes an acyl group can be prepared by any esterification method, by means of which the R group can be introduced, from the racemic mixture of the compounds of the general formula I, in which R denotes hydrogen.
  • the esterification is effected by converting a racemic mixture of a compound of the general formula I, in which R denotes hydrogen, with a carboxylic acid anhydride or carboxylic acid chloride in the presence of bases such as pyridine, triethylamine, dimethylaminopyridine.
  • a racemic mixture of a compound of the general formula I is introduced into a diluting agent.
  • R denotes an acyl group
  • no esterifying agent is added.
  • water or an aqueous salt or buffer solution, preferably a phosphate buffer, which exhibits a pH value that is optimal for the esterase used, is used as the diluent.
  • the buffer solution can be added as such or together with organic diluents.
  • Suitable organic diluents are, for example, aliphatic or aromatic hydrocarbons such as hexane, toluene, xylenes, ethers such as diethyl ether, diisopropyl ether, tert.-butyl-methyl-ether, tetrahydrofuran, ketones such as acetone, butanone, tert.-butyl-methyl-ketone or mixtures of such diluents.
  • ethers such as diethyl ether, diisopropyl ether, tert.-butyl-methyl-ether, tetrahydrofuran, ketones such as acetone, butanone, tert.-butyl-methyl-ketone or mixtures of such diluents.
  • ketones such as acetone, butanone, tert.-butyl-methyl-ketone or mixtures of such diluents.
  • esterifying agent is added to the starting racemic mixture.
  • esterifying agents such as carboxylic acid esters, for example compounds of the general formula R 5 COOR 6 , in which R 5 and R 6 denote independently of each other alkyl, aryl or aralkyl groups, carboxylic acid ester of multivalent alcohols, for example glycerol triacylates such as glycerol triacetate, glycerol tributyrate, carboxylic acid anhydrides, as disclosed, for example, in the EP-A-0 269 453, or vinyl esters, for example, according to the U.S. Pat No. 4,963,492, can be used as esterifying agents.
  • a carboxylic acid ester of the general formula R 5 COOR 6 in which R 5 and R 6 denote independently of each other an alkyl group having 1 to 6 C atoms; a glycerol triacylate; a vinyl ester of the general formula CH 2 ⁇ CH--O--CO--R 7 , in which R 7 denotes hydrogen, an alkyl group having 1 to 18 C atoms or a phenyl group, especially preferred an alkyl group having 1 to 6 C atoms; a carboxylic acid anhydride of the general formula R 8 --CO--O--CO--R 9 , in which R 8 and R 9 are the same or not the same, preferably the same and denote an alkyl, aryl or aralkyl group, especially preferred an alkyl group having 1 to 6 C atoms, is added as the esterifying agent.
  • suitable diluents are inert diluents, for example aliphatic or aromatic hydrocarbons such as hexane, toluene, xylene, ethers such as diethyl ether, diisopropyl ether, tert.-butyl-methyl-ether, ketones such as tert.-butyl-methyl-ketone, also the esterifying agent itself or mixtures of the aforementioned diluents.
  • inert diluents for example aliphatic or aromatic hydrocarbons such as hexane, toluene, xylene, ethers such as diethyl ether, diisopropyl ether, tert.-butyl-methyl-ether, ketones such as tert.-butyl-methyl-ketone, also the esterifying agent itself or mixtures of the aforementioned diluents.
  • At least one half equivalent, preferably 1 to 8 equivalents of the esterifying agent, is added per equivalent of the racemic mixture with the general formula I, in which R denotes hydrogen.
  • R denotes hydrogen.
  • the esterifying agent is also added preferably simultaneously as the diluent, whereby a very high excess of the esterifying agent is added.
  • a base for example potassium or sodium hydrogen carbonate, is added to the reaction mixture in order to bond the resulting acid.
  • hydrolases are understood, e.g. lipases, esterases, proteases. Preferred are lipases, especially preferred lipases of the microorganisms Alcaligenes, Pseudomonas, Candida, Mucor.
  • the hydrolase can be added as cleaned enzyme fractions or as a suspension of microorganisms, which contains the hydrolase, but is added preferably as a cleaned enzyme fraction.
  • the hydrolase can be added as such or immobilized; that means, physically or chemically bonded to a carrier.
  • Hydrolases can be bought and with respect to the reaction conditions are added advantageously according to the instructions of the seller.
  • the hydrolase suffers virtually no noteworthy loss in activity and can, therefore, be added repeatedly.
  • the suitable quantity of hydrolase depends on the chemical nature of the starting compound used, the hydrolase used, the diluent used and the optional esterifying agent and can be readily determined by pilot tests. Since the added hydrolase is reusable, a large quantity of hydrolase can be added without harm in those cases in which a large quantity of hydrolase has a good effect on the reaction speed, without rendering the process costs notably expensive. Preferably about 0.05 to 2 g of hydrolase are added per gram of starting compound of the general formula I.
  • hydrolases can both link and break ester bonds, they can carry out both the selective hydrolysis of the compounds of the general formula I, in which R denotes an acyl group and the selective esterification of the compounds of the general formula I, in which R denotes hydrogen.
  • reaction temperature preferably that temperature is selected at which the hydrolase shows its highest activity. This temperature is generally noted for commercially available hydrolases and can otherwise be readily determined by simple pilot tests.
  • the reaction temperature ranges from -10° C. to the deactivation temperature of the added hydrolase, depending on the hydrolase used and depending on the substrate used. Generally the reaction temperature ranges from room temperature to 60° C.
  • the hydrolase produces a reaction mixture containing an enantiomerically pure beta-hydroxy-delta-valerolactoae and an enantiomerically pure beta-acyloxy-delta-valerolactone.
  • a vinyl ester as the esterifying agent, the reaction is finished totally unexpected in a very short period of time. The reaction proceeds with virtually 100% selectivity, since it has been found that the reaction comes to an end by itself after conversion of one of the enantiomers.
  • the conversion can be followed by simple thin layer or gas chromatography and it is not necessary, as in the case of less selective reactions, to break off the reaction at a specific degree of conversion, in order to prevent overreaction and contamination of the desired product. Since enzymes exhibit only very rarely such a high selectivity and since it is known in particular of lipases that they prefer one enantiomer during conversions, but that they also generally convert the second enantiomer, as soon as the substrate is impoverished of the preferred enantiomer, the high selectivity of the reaction of the invention is extremely surprising.
  • the desired enantiomer is subsequently separated from the reaction mixture. Since the one enantiomer in the reaction mixture is a compound with a free and the second enantiomer is a compound with an acylated hydroxy group, the separation is very simple to perform and can be conducted by known methods such as crystallization, extraction, distillation, chromatography.
  • Enantiomerically pure compounds of the general formula I, in which R denotes an acyl group and in which R 1 and R 2 have the aforementioned meaning are, with the exception of (2S,3S,5R)-2-hexyl-3-benzoyloxy-5-undecyl-delta-valerolactone, which is described in the ZA 91/1153, are new and also object of the invention.
  • the separated compounds can be subsequently purified still further by conventional methods such as crystallization, recrystallization, chromatography.
  • a racemic mixture of a compound of the general formula I, in which R 1 and R 2 denote alkyl groups having 4 to 20 C atoms and R denotes an acyl group is suspended in a sodium phosphate buffer at pH 7 with the addition of an organic diluent.
  • the reaction mixture is brought into contact with a lipase at temperatures ranging from room temperature to 60° C., whereby either the lipase is added to the reaction mixture, or the reaction mixture is pumped continuously over a lipase, which is insoluble in the reaction, preferably over an immobilized lipase.
  • the pH value of the reaction mixture is held constant through the addition of an aqueous base.
  • the course of the reaction is followed by means of chromatography or with the aid of the quantity of the consumed base.
  • the mixture that is obtained and contains a virtually enantiomerically pure beta-hydroxy-delta-valerolactone and a virtually enantiomerically pure beta-acyloxy-delta-valerolactone is separated by simply cooling the reaction mixture, whereby the hydroxy compound precipitates as crystals, whereas the acyloxy compound remains in solution.
  • a racemic mixture of a compound of the general formula I in which R denotes hydrogen and R 1 and R 2 denote alkyl groups having 4 to 20 C atoms, is dissolved or suspended in a carboxylic acid ester of the general formula R 5 COOR 6 , a vinyl alkanoate of the general formula CH 2 ⁇ CH--O--COR 7 or a carboxyl acid anhydride of the general formula R 8 --CO--O--CO--R 9 , in which R 5 , R 6 , R 7 , R 8 and R 9 denote an alkyl group having 1 to 6 C atoms, or in a glycerol triacylate, especially preferred in glycerol triacetate, glycerol tributyrate, vinyl acetate, acetic anhydride, propionic acid anhydride or ethyl acetate, if desired with the use of an inert diluent.
  • R 5 COOR 6 a vinyl alkanoate of the
  • a base for example potassiumhydrogen carbonate
  • the reaction mixture is cooled, whereby the virtually enantiomerically pure beta-hydroxy-delta-valerolactone precipitates as crystals out of the reaction mixture, or the diluent and the esterifying agent are evaporated at the rotary evaporator and the beta-hydroxy-delta-valerolactone is separated from the residue by crystallizing or recrystallizing the beta-acyloxy-delta-valerolactone.
  • the process yields pure enantiomers of beta-hydroxy- and beta-acyloxy-delta-valerolactones. In so doing, it depends on the specificity of the hydrolase used, whether the (2R,3R,5S)-enantiomer or the (2S,3S,5R)-enantiomer in the racemic mixture is converted.
  • both the reacted and the unreacted enantiomer can be further used. If a desired enantiomer is produced as the acylated product, it can be readily transformed into a desired enantiomerically pure beta-hydroxy-valerolactone by splitting off the acyl group, for example, through alkaline hydrolysis.
  • Such oxetanones are used for the preparation of lipase inhibitors, especially for the preparation of N-formyl-L-leucine-(S)-1-(((2S,3S)-3-hexyl-4-oxooxetane-2-yl)-methyl)-dodecylester of the formula ##STR3## which is known under the trivial name tetrahydrolipstatin (THL).
  • TTL tetrahydrolipstatin
  • a preparation of oxetanones of the formula II as well as a preparation of THL via a delta-valerolactone are described in the ZA 91/1153.
  • the process according to the invention in a process for the preparation of an oxetanone of the formula II from a delta-valerolactone of the formula ##STR4## as well as a process for the preparation of THL of the formula IV from the delta-valerolactone of the formula ##STR5## via the oxetanone of the formula ##STR6## for providing said compounds in the enantiomerically pure form are also subject of the invention.
  • race-(2RS,3RS,5SR)-2-hexyl-3-hydroxy-5-undecyl-delta-valerolactone (0.33 mmol) (IUPAC: race-(1,u)-3-hexyl-4-hydroxy-6-undecyl-3,4,5,6-tetrahydropyran-2-one) were suspended in 2 ml of vinyl acetate and treated with 0.1 g of lipase from Candida cylindracea. The incubation occurred at room temperature on an agitator at 230 rpm. The course of the reaction was followed by thin layer chromatography.
  • the amount of optical rotation of the acetate-alpha D 20 - was -65°; the melting point, 93° C., which corresponds to the theoretical values.
  • (2R,3R,5S)-2-hexyl-3-acetoxy-5-undecyl-delta-valerolactone was obtained with an alpha D 20 of -65.3° and a melting point of 93° C.
  • (2S,3S,5R)-2-hexyl-3-hydroxy-5-undecyl-delta-valerolactone was obtained with alpha D 20 of +49.7° (theoretic: +48° to +50°) and a melting point of 108° C. (theoretic: 106°-108° C.).
  • reaction mixture After addition of 0.5 g of lipase from Pseudomonas, the reaction mixture was incubated at 40° C., whereby the pH value was held constant through continuous addition of an aqueous, 0.1 m sodium hydroxide solution. The reaction was controlled by means of thin layer chromatography and with the aid of the consumed sodium hydroxide solution.
  • reaction mixture was extracted with ethyl acetate and the organic phase was dried over sodium sulfate and evaporated. The residue was recrystallized from vinyl acetate.
  • reaction mixture was cooled to 10° C., whereby 480 mg, which is 48% of the theoretical, crystalline, pure (2S,3S,5R)-2-hexyl-3-hydroxy-5-undecyl-delta-valerolactone were obtained.
  • the yields, which are given in the examples, are always based on the quantity of pure enantiomer added in the starting racemic mixture.
  • the enantiomeric purity of (2S,3S,5R) and of 2R,3R,5S)-2-hexyl-3-acetoxy-5-undecyl-delta-valerolactone was determined by means of 1 HNMR using tris(3-(2,2,2,-trifluoro-1-hydroxyethylidene)-d-camphorat)-europium.
  • the amount of optical rotation alpha D 20 was for the (2R,3R,5S) compound -65° and for the (2S,3S,5R) compound +65°.
  • the melting point was 93° C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US07/936,782 1992-07-06 1992-08-28 Enzymatic process to separate racemic mixtures of delta valerolactones Expired - Fee Related US5412110A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT0137492A AT398579B (de) 1992-07-06 1992-07-06 Enzymatisches verfahren zur trennung racemischer gemische von delta-valerolactonen
AT1374/92 1992-07-06

Publications (1)

Publication Number Publication Date
US5412110A true US5412110A (en) 1995-05-02

Family

ID=3512505

Family Applications (1)

Application Number Title Priority Date Filing Date
US07/936,782 Expired - Fee Related US5412110A (en) 1992-07-06 1992-08-28 Enzymatic process to separate racemic mixtures of delta valerolactones

Country Status (23)

Country Link
US (1) US5412110A (cs)
EP (1) EP0578016A3 (cs)
JP (1) JPH06153988A (cs)
KR (1) KR940005806A (cs)
CN (1) CN1082113A (cs)
AT (1) AT398579B (cs)
AU (1) AU670088B2 (cs)
BR (1) BR9302763A (cs)
CA (1) CA2096597A1 (cs)
CZ (1) CZ133293A3 (cs)
FI (1) FI933079A (cs)
HR (1) HRP931019A2 (cs)
HU (1) HUT67439A (cs)
IL (1) IL105720A (cs)
MX (1) MX9304057A (cs)
MY (1) MY109188A (cs)
NO (1) NO932030L (cs)
NZ (1) NZ247636A (cs)
SI (1) SI9300361A (cs)
SK (1) SK69793A3 (cs)
TR (1) TR27224A (cs)
YU (1) YU40493A (cs)
ZA (1) ZA933682B (cs)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6020500A (en) * 1995-08-22 2000-02-01 The Lubrizol Corporation Hydroxy-substituted monolactones useful as intermediates for preparing lubricating oil and fuel additives
WO2005005403A2 (en) * 2003-07-15 2005-01-20 Ranbaxy Laboratories Limited Process for preparation of oxetan-2-ones

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100238290B1 (ko) * 1997-06-16 2000-01-15 윤종용 테이프 레코더의 릴디스크 제동장치
JPH11165762A (ja) * 1997-12-01 1999-06-22 Lintec Corp チップ体搬送用カバーテープおよび封止構造体
KR101035526B1 (ko) * 2004-04-26 2011-05-23 덴끼 가가꾸 고교 가부시키가이샤 커버 테이프 및 전자 부품 포장용 캐리어 테이프 시스템
KR101145344B1 (ko) * 2010-04-09 2012-05-14 박진성 전자 부품 이송용 커버 테이프

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0269453A2 (en) * 1986-11-28 1988-06-01 Takeda Chemical Industries, Ltd. A process for producing carboxylic acid esters
US4963492A (en) * 1987-12-23 1990-10-16 Hoechst Aktiengesellschaft Method for the enzymatic racemate resolution of racemic alcohols with/in vinyl esters by transesterification
EP0439779A2 (en) * 1990-02-02 1991-08-07 Chisso Corporation Process for producing optically active hydroxy lactones
ZA911153B (en) * 1990-02-23 1991-11-27 Hoffmann La Roche Process for the preparation of oxetanones

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4005150A1 (de) * 1990-02-17 1991-08-22 Hoechst Ag Verfahren zur enzymatischen racematspaltung von pantolacton
CA2118795A1 (en) * 1991-09-20 1993-04-01 John Crosby Pyranones
WO1993006235A1 (en) * 1991-09-20 1993-04-01 Zeneca Limited Process for the preparation of enantiomerically pure 4-hydroxytetrahydro-2-pyranone derivatives
DE4225817A1 (de) * 1992-08-05 1994-02-10 Chemie Linz Deutschland Enzymatisches Verfahren zur Trennung racemischer Gemische von delta-Valerolactonen

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0269453A2 (en) * 1986-11-28 1988-06-01 Takeda Chemical Industries, Ltd. A process for producing carboxylic acid esters
US4963492A (en) * 1987-12-23 1990-10-16 Hoechst Aktiengesellschaft Method for the enzymatic racemate resolution of racemic alcohols with/in vinyl esters by transesterification
EP0439779A2 (en) * 1990-02-02 1991-08-07 Chisso Corporation Process for producing optically active hydroxy lactones
US5084392A (en) * 1990-02-02 1992-01-28 Chisso Corporation Process for producing optically active hydroxy lactones
ZA911153B (en) * 1990-02-23 1991-11-27 Hoffmann La Roche Process for the preparation of oxetanones

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Laymen et al, J. Chem. Soc., Chem. Commun. (1988), pp. 1459 1461. *
Laymen et al, J. Chem. Soc., Chem. Commun. (1988), pp. 1459-1461.

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6020500A (en) * 1995-08-22 2000-02-01 The Lubrizol Corporation Hydroxy-substituted monolactones useful as intermediates for preparing lubricating oil and fuel additives
US6114547A (en) * 1995-08-22 2000-09-05 The Lubrizol Corporation Hydroxy-substituted monolactones and use thereof as intermediates for preparing lubricating oil and fuel additives
WO2005005403A2 (en) * 2003-07-15 2005-01-20 Ranbaxy Laboratories Limited Process for preparation of oxetan-2-ones
WO2005005403A3 (en) * 2003-07-15 2005-04-07 Ranbaxy Lab Ltd Process for preparation of oxetan-2-ones

Also Published As

Publication number Publication date
NO932030L (no) 1994-01-07
MY109188A (en) 1996-12-31
SI9300361A (en) 1994-03-31
AU670088B2 (en) 1996-07-04
TR27224A (tr) 1994-12-20
FI933079A0 (fi) 1993-07-05
EP0578016A3 (en) 1995-03-01
ZA933682B (en) 1993-12-21
HRP931019A2 (en) 1997-04-30
CZ133293A3 (en) 1994-02-16
BR9302763A (pt) 1994-02-16
KR940005806A (ko) 1994-03-22
JPH06153988A (ja) 1994-06-03
MX9304057A (es) 1994-02-28
CA2096597A1 (en) 1994-01-07
HUT67439A (en) 1995-04-28
NO932030D0 (no) 1993-06-03
HU9301956D0 (en) 1993-10-28
ATA137492A (de) 1994-05-15
YU40493A (sh) 1996-07-24
IL105720A0 (en) 1993-09-22
IL105720A (en) 1998-01-04
FI933079A (fi) 1994-01-07
NZ247636A (en) 1995-04-27
SK69793A3 (en) 1994-05-11
AT398579B (de) 1994-12-27
EP0578016A2 (de) 1994-01-12
CN1082113A (zh) 1994-02-16
AU4132593A (en) 1994-01-13

Similar Documents

Publication Publication Date Title
US5538891A (en) Process for enzymatic production of isomerically pure isosorbide-2 and 5-monoesters and their conversion to isosorbide-2 and -5 nitrate
US5412110A (en) Enzymatic process to separate racemic mixtures of delta valerolactones
EP0274277B1 (en) A process for the enzymatic separation of the optical isomers of racemic oxazolidinonic derivatives
US5169779A (en) Process for the preparation of methyl (-)-(2R,3S)-2,3-epoxy-3-(4-methoxy-phenyl)propionate
US5266710A (en) (Exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol; monoacyl ester and diacyl ester
CZ191698A3 (cs) Způsob přípravy meziproduktů pro syntézu činidel účinných proti houbám
US4863859A (en) Process for preparing optically active glycerol derivatives
US5326885A (en) Process of preparing enriched enantiomers of glycerol carbonate and derivatives thereof for synthesis of β-blockers
US4922001A (en) Chiral synthesis units from prochiral glycerol
EP0435293B1 (en) Methods of producing optically active hydroxyesters
US5084387A (en) Microbiological hydrolysis for the preparation of (exo,exo)-7-oxabicyclo(2.2.1) heptane-2,3, monoacyl ester dimethanol
US5756830A (en) Process for preparing intermediates for the synthesis of antifungal agents
JPH05227991A (ja) 光学活性な３−ピロリジノール誘導体の製造法
IE903437A1 (en) Enantioselective enzymatic synthesis of s(-)- and¹r(+)-esters of 4-hydroxy-2-cyclopenten-1-one and its ketal¹formed with 2,2-dimethyl- propane-1,3-diol
JP2689478B2 (ja) 光学活性なフェネチルアルコール誘導体の製法
NO172903B (no) Fremgangsmaate for fremstilling av optisk aktive (+)-bicyklo(3.3.0)oktanol-derivater
JP3010382B2 (ja) （ｒ）−２−プロポキシベンゼン誘導体の製造法
JPH0632633B2 (ja) 光学活性カルボン酸の製造法
JP3158700B2 (ja) 光学活性なｅｘｏ−３−アリル−ｅｎｄｏ−２−ノルボルナノールの製造法
DE4225817A1 (de) Enzymatisches Verfahren zur Trennung racemischer Gemische von delta-Valerolactonen
JPH05268978A (ja) 異性体上純粋なイソソルビド−２−および−５− モノエステルの酵素的製造法並びにイソソルビド −２−および−５−ニトレートへのそれらの変換
HU216797B (hu) Eljárás a (2S, 3S)-treo-2-hidroxi-3-(4-metoxi-fenil)-3-(fenil-tio)- és (2R, 3R)-treo-2-alkanoil-oxi-3-(4-metoxi-fenil)-3-(fenil-tio)-propionát-származékok előállítására
JPH01247100A (ja) 光学活性カルボン酸誘導体の製造方法
JPH0513636B2 (cs)
JPH07322889A (ja) 光学活性な２，５−ピロリジンジオン誘導体の製造法

Legal Events

Date Code Title Description
AS Assignment

Owner name: CHEMIE LINZ GESELLSCHAFT M.B.H., STATELESS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:POCHLAUER, PETER;WAGNER, MARION;REEL/FRAME:006257/0813

Effective date: 19920812

Owner name: CHEMIE LINZ GESELLSCHAFT M.B.H., AUSTRIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:POCHLAUER, PETER;WAGNER, MARION;REEL/FRAME:006257/0813

Effective date: 19920812

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

REFU Refund

Free format text: REFUND - PAYMENT OF MAINTENANCE FEE, 4TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: R183); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

LAPS Lapse for failure to pay maintenance fees
FP Lapsed due to failure to pay maintenance fee

Effective date: 19990502

STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362